DESCRIPTION: Dr. Hortsch proposes to continue his investigation of the mechanism by which neuroglian/L1-CAM recruits ankyrin to the vicinity of the plasma membrane in Drosophila embryos and transfected S2 cells. He proposes a number of straightforward deletion and replacement mutagenesis studies to analyze which domains of neuroglian are required to recruit ankyrin. He also will use yeast two-hybrid and ankyrin affinity chromatography approaches to identify additional ankyrin-binding membrane proteins in Drosophila and will use transgenic Drosophila lines containing myc-tagged ankyrin to demonstrate the in vivo effects of neuroglian mutants. Finally, he will use this assay system to test whether mutant L1-CAM molecules from human patients will function in his assay.